Comparative assessment of poly (D,L-lactide-co-glycolide) nanoparticles modified by either cetyltrimethylammonium bromide or chitosan for plasmid DNA adsorption

Abd Almonem Doolaanea,Susi Sukmasari,Farahidah Mohamed,Nur ‘Izzati Mansor,Mohd Affendi Bin Mohd Shafri,Nurul Hafizah Mohd Nor

doi:10.4314/tjpr.v16i10.2

Abstract

Purpose: To evaluate poly (D,L-lactide-co-glycolide) PLGA nanoparticles modified by cetyltrimethyl ammonium bromide (CTAB) or chitosan for plasmid DNA adsorption.Methods: PLGA nanoparticles were prepared by solvent diffusion method and modified by including CTAB in the aqueous (F1) or oil phase (F2), or by including low (F3) or medium (F4) molecular weight chitosan. The nanoparticles were characterised by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), as well as for cell toxicity, cell uptake and transfection.Results: CTAB failed to confer positive charge on the nanoparticles. CTAB desorbed easily from F1 surface. This resulted in negative zeta potential, increased cytotoxicity as well as decreased cell uptake and transfection. In F2, CTAB was located mainly in PLGA matrix, resulting in negative charge with decreased cytotoxicity, and increased cell uptake and transfection compared to F1. On the other hand, chitosan-modified nanoparticles (F3 and F4) showed stronger interaction between chitosan and PLGA, leading to positively-charged particles, decreased cytotoxicity, as well as increased cell uptake and transfection. Amongst the four formulations, F4 exhibited the highest transfection.Conclusion: These results should aid in understanding how PLGA nanoparticles are modified by CTAB and chitosan. Modification with chitosan yields PLGA nanoparticles with higher DNA adsorption and transfection with lower cytotoxicity.Keywords: Chitosan, cetyltrimethyl ammonium bromide (CTAB), Nanoparticle, Poly (D,L-lactide-coglycolide) PLGA, Plasmid DNA adsorption, Gene therapy

Highlights

(D, L-Lactic-co-Glycolic Acid) polymer (PLGA) is biodegradable and biocompatible polymer widely used in microencapsulation
To compare chitosan and cetyltrimethyl ammonium bromide (CTAB), this study aimed to prepare PLGA nanoparticles modified with either CTAB or chitosan in total four formulations
CTAB content of the nanoparticles is larger in F2 compared to F1 and as a result, the Tg of F2 was slightly higher than the Tg of F1 (43.8 °C compared to 43.3 °C)

Summary

Introduction

(D, L-Lactic-co-Glycolic Acid) polymer (PLGA) is biodegradable and biocompatible polymer widely used in microencapsulation. Its robust synthetic pathway allows constructing variety of sustained release drug delivery devices [1,2]. PLGA nanoparticles and microparticles have been frequently used to deliver nucleic acids after being modified to become positively charged [3]. The positively charged particles interact with the negatively charged nucleic acids by means of electrostatic interactions to make a stable complex that can protect and deliver DNA or RNA. Nanoparticles with positive charge are more effective than negatively charged ones in the lysosomal escape [4]. Some of the commonly used surface modifying materials include chitosan [3] and cetyltrimethylammonium bromide (CTAB) [5]

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